Starting my ‘on call’ week tomorrow and super looking forward to it 🙂
Definition: rare inherited disorder of biliary copper excretion with to much copper (Cu) in the liver and central nervous system, especially in the basal ganglia. Also known as hepatolenticular degeneration.
Aetiology/ risk factors:
-autosomal recessive disorder of a gene on chromosome 13 that codes for a copper transporting ATPase- ATP7B.
-More than 200 mutations are known. HIS1069GLU is the commonest in European populations.
Epidemiology: rare- 3 in 100,000
Symptoms & Signs:
-Children present with liver disease (hepatitis, cirrhosis, fulminant liver failure) and the signs and symptoms this entails.
-Young adults often start with CNS signs:
–dysarthria (motor speech disorder resulting in slurred speech),
–dysphagia (difficulty swallowing),
–dyskinesias (abnormality or impairment of voluntary movement),
–dystonias (movement disorders that cause muscle spasms and contractions),
–purposeless stereotyped movements e.g. hand clapping,
–parkinsonism (bradykinesia, shuffling gait, posture abnormalities),
–microgaphia (small handwriting),
-increased or decreased libido
-quick to anger
-slow problem solving
-Kayser-Fleischer rings = copper in iris
Urine- 24h copper excretion is high (e,g, > 100 μg/24h, normal is < 40)
LFTs- enzymes increased but non-specific pattern
Serum copper- low, typically < 11μmol/l
Serum caeruloplasmin- low < 200mg/L (< 140mg/L is characteristic)
Caeruloplasmin is a carrier molecule for copper in the blood. In the liver, copper is incorporated into caeruloplasmin, but in Wilson’s this incorporation, and the excretion of copper into bile, is impaired, leading to copper accumulation in the liver and later, in other organs.
It is a protein produced in the liver, so can also be low in protein deficiency states and any chronic liver disease that causes a decrease in synthesis. It is also an acute phase protein, so is sometimes high in infection, inflammation and pregnancy.
Molecular genetic testing- can confirm diagnosis
Slit lamp exam-see KF rings in the iris/ Descemet’s membrane (= deposition of copper in part of the cornea called Descemet’s membrane)
May see sunflower cataract (copper in the lens)
Liver biopsy- increased hepatic copper, hepatitis, cirrhosis
MRI- degeneration in basal ganglia, fronto-temporal, cerebellar and brainstem.
-Wilson’s is treatable so all young people with liver cirrhosis should be screened, as should siblings of diagnosed patient.
-Avoid eating foods with a high copper content e.g. liver, chocolate, nuts, mushrooms, legumes, shellfish
-Lifelong penicillamine (chelating agent) (500mg/6-8h PO for 1yr, maintenance 0.75-1g/d)
Side effects: nausea, rash, anaemia, reduced white cells and platelets, haematuria, nephrotic syndrome, lupus
Monitor FBC & urinary copper. Stop if white cells or platelets too low.
-Alternative = trientine dihydrochloride (600mg/6-12h PO)
–Liver transplant if severe liver disease.
-liver cirrhosis, liver failure
-permanent CNS damage
-gallstones (caused by haemolysis)
-copper induced renal tubular damage causing hypercalciuria, phosphaturia and osteomalacia
-renal tubular acidosis
-bleeding and infection- due to low platelets and white cells on penicillamine
Prognosis: pre-cirrhotic liver disease is reversible, CNS damage is less so
References: Cheese & Onion, Rapid Medicine